Proton-Bound Dimers of Nitrogen Heterocyclic Molecules: Substituent

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2014 Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine Isaac K. Attah Virginia Commonwealth University, [email protected]

Sean P. Platt Virginia Commonwealth University, [email protected]

Michael Mautner Virginia Commonwealth University, [email protected]

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Attah, I. K., Platt, S. P., & Mautner, M., et al. Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine. The ourJ nal of Chemical Physics, 140, 114313 (2014). Copyright © 2014 AIP Publishing LLC.

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Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and ﬂuoropyridine Isaac K. Attah,1 Sean P. Platt,1 Michael Meot-Ner (Mautner),1 M. S. El-Shall,1,a) Saadullah G. Aziz,2 and Abdulrahman O. Alyoubi2 1Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284-2006, USA 2Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia (Received 3 January 2014; accepted 19 February 2014; published online 21 March 2014)

The bonding energies of proton-bound homodimers BH+B were measured by ion mobility equilibrium studies and calculated at the DFT B3LYP/6-311++G∗∗ level, for a series of nitrogen heterocyclic molecules (B) with electron-withdrawing in-ring N and on-ring F substituents. The ◦ + binding energies (H dissoc) of the proton-bound dimers (BH B) vary significantly, from 29.7 to 18.1 kcal/mol, decreasing linearly with decreasing the proton affinity of the monomer (B). This trend differs significantly from the constant binding energies of most homodimers of other or- ◦ + ganic nitrogen and oxygen bases. The experimentally measured H dissoc for (1,3-diazine)2H , + + i.e., (pyrimidine)2H and (3-F-pyridine)2H are 22.7 and 23.0 kcal/mol, respectively. The mea- ◦ ·+ sured H dissoc for the pyrimidine (3-F-pyridine) radical cation dimer (19.2 kcal/mol) is signifcantly lower than that of the proton-bound homodimers of pyrimidine and 3-F-pyridine, reflect- ing the stronger interaction in the ionic H-bond of the protonated dimers. The calculated bind- + + + + ing energies for (1,2-diazine)2H , (pyridine)2H , (2-F-pyridine)2H , (3-F-pyridine)2H , (2,6-di- + + + + + F-pyridine)2H , (4-F-pyridine)2H , (1,3-diazine)2H , (1,4-diazine)2H , (1,3,5-triazine)2H , and + (pentafluoropyridine)2H are 29.7, 24.9, 24.8, 23.3, 23.2, 23.0, 22.4, 21.9, 19.3, and 18.1 kcal/mol, respectively. The electron-withdrawing substituents form internal dipoles whose electrostatic interactions contribute to both the decreased proton affinities of (B) and the decreased binding energies of the protonated dimers BH+B. The bonding energies also vary with rotation about the hydrogen bond, and they decrease in rotamers where the internal dipoles of the components are aligned efficiently for inter-ring repulsion. For compounds substituted at the 3 or 4 (meta or para) positions, the lowest energy rotamers are T-shaped with the planes of the two rings rotated by 90◦ about the hydrogen bond, while the planar rotamers are weakened by repulsion between the ortho hydrogen + + atoms of the two rings. Conversely, in ortho-substituted (1,2-diazine)2H and (2-F-pyridine)2H , attractive interactions between the ortho (C–H) hydrogen atoms of one ring and the electronegative ortho atoms (N or F) of the other ring are stabilizing, and increase the protonated dimer binding energies by up to 4 kcal/mol. In all of the dimers, rotation about the hydrogen bond can involve a 2–4 kcal/mol barrier due to the relative energies of the rotamers. © 2014 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4867288]

I. INTRODUCTION thermochemistry of hydrogen bonded heterodimers AH+·B = Aromatic nitrogen heterocyclic compounds occur in en- (where B H2O) of nitrogen heterocyclics was studied vironments ranging from biochemistry and pharmacology to in pyridine derivatives with electron donating or withdraw- synthetic chemistry, environmental chemistry, meteorites, in- ing substituents, and several structural features have been terstellar clouds, astrochemistry, and astrobiology.1–5 These identiﬁed including steric effects in hindered alkylpyridines nitrogen bases can be protonated in solution by acids, and in and multiple hydrogen bonds in protonated dimers of nu- 7, 9, 12 +· the gas phase through ions produced by radiation. The proto- cleic bases. A general feature of these AH Bdimers nated bases can then form strong ionic hydrogen bonds with (Eq. (1)) is an inverse relation between the differences neutral solvent molecules or bases, including neutral nitrogen of the proton afﬁnities of A and B molecules (i.e., PA = − heterocyclics.4, 5 These hydrogen bonds contribute to ion sol- PA(A) PA(B)) and the ionic hydrogen bond strength (i.e., − ◦ +· vation, and biological and crystal structures. Complexes with H D(AH B)) as shown by Eq. (2). This inverse relation- strong ionic hydrogen bonds were reviewed recently.6 ship has been observed for protonated dimers of various ni- An important class of ionic hydrogen bonded systems trogen, oxygen, and sulfur bases over PA differences as large 7, 11, 13 is the proton-bound dimers where a bridging proton con- as 60 kcal/mol: 7–26 nects two electronegative centers in two molecules. The AH+ + B → AH+·B, (1) a) Author to whom correspondence should be addressed. Electronic mail: ◦ + [email protected] − H D(AH ·B) = a − b PA, (2)

This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditions. Downloaded to IP: 128.172.48.59 On: Mon, 12 Oct 2015 17:07:39 114313-2 Attah et al. J. Chem. Phys. 140, 114313 (2014)

where a and b are parameters obtained from the linear fit- homodimers of the azines and flurobenzenes with electron- ◦ + ting of −H D(AH ·B) and PA. For nitrogen bases such withdrawing substituents. as amines and pyridines, a is usually 24 ± 1 kcal/mol and b is about 0.3. Therefore, for homodimers, where PA = 0, this II. EXPERIMENTAL SECTION empirical relation predicts H◦ (BH+·B) = 24 ± 1 kcal/mol D The equilibrium thermochemical measurements reported for all of these bases regardless of the absolute proton affini- here were carried out using the Virginia Commonwealth Uni- ties of the bases. versity (VCU) mass-selected ion mobility mass spectrom- In such homodimers B H+ (i.e., BH+·B), the proton 2 eter. Details of the instrument were given in Refs. 30–34. is shared efficiently between the two components which of The pyrimidine (1,3-diazine) and 3-F-pyridine radical cations course have equal proton affinities. As PA(B) increases, the were generated by 70 eV electron impact ionization of the protonated component (BH+) becomes a less efficient proton neutral monomers that were introduced to the ion source donor, weakening the hydrogen bond (BH+···B), while the by supersonic expansion of 40 psi (2.8 bars) of ultra-pure neutral component (B) becomes a more efficient proton ac- helium seeded with about 1%–4% of vapor of the corre- ceptor because of the increased PA, thus strengthening the sponding compound (pyrimidine and 3-fluoropyridine, re- bond.1, 7, 11, 14 These effects can cancel and the dissociation spectively) through a pulsed supersonic nozzle (500 μm) to energies H◦ (B H+) remain nearly constant for homod- D 2 the vacuum source chamber with 10−7 Torr pressure. The rad- imers B H+ regardless of the proton affinity of the monomer, 2 ical cations were then mass selected using a first quadrupole PA(B). For alkylamine and alkylpyridine bases H◦ (B H+) D 2 mass-filter, and injected in 30–50 μs pulses into the drift cell. is nearly constant at 24 ± 2 kcal/mol for compounds with The ions are injected into the mobility cell with injection en- proton affinities ranging over 30 kcal/mol. For example, for ergies of 8–14 eV, laboratory frame, just above the minimum both (NH ) H+ and (pyridine) H+ the binding energy is 24 3 2 2 energies required to introduce the ions into the cell against the ± 2 kcal/mol although PA(B) changes from PA(NH ) = 204 3 backward flow of the gas mixture from the drift cell entrance kcal/mol to PA(pyridine) = 222 kcal/mol, and the structures orifice. Most of the thermalization of the injected ion occurs of the bases are also very different.1, 27 Similarly, for oxygen just outside the cell entrance by collisions with the monomer bases with different PAs over a range of 40 kcal/mol, bond en- molecules and He atoms escaping from the cell.30–32 Further ergies of the protonated homodimers are nearly constant be- thermalization occurs in the mobility cell. For example, at a tween 30 and 32 kcal/mol.12, 14, 28 cell pressure of 0.2 Torr, the number of collisions of an ion However, the bonding energies can be affected by struc- with the neutral molecules within the 1.5 ms residence time tural effects. For example, multiple hydrogen bonds in the inside the cell is about 104 collisions.30–32 The number of col- protonated dimers of nucleic bases increase the dimer bond- lisions necessary for thermalization (about 100) can therefore ing energies by up to 6 kcal/mol per extra bond.9, 15 An- occur within the first 1% of the ion drift time or distance. other structural effect was observed in dimer ions of 2,6- The reaction mixture in the cell contained a neutral alkylpyridines with bulky alkyl substituents. The hydrogen monomer/helium buffer gas mixture. A constant concentra- bonds were not strained even with bulky ortho substituents, tion of the neutral monomer in the drift cell was main- but steric hindrance to rotation about the hydrogen bond leads tained using flow controllers (MKS #1479A), which are ac- to large negative entropy change upon dimer formation.12, 29 curate to within ±1 mTorr. The drift cell temperature was In the present work, we examine protonated homod- controlled within ±1 K using four temperature controllers. imers of aromatic nitrogen heterocyclics, i.e., diazines (1,2- The injected radical ions react with the neutral molecules diazine, 1,3-diazine, and 1,4-diazine), 1,3,5-triazine, and in the drift cell through self-protonation forming the proto- also some fluoropyridines (2-F-pyridine, 3-F-pyridine, 4- nated monomer, followed by association to form the pro- F-pyridine, 2,6-difluoro-pyridine, and pentafluoro-pyridine). tonated dimer. An alternative method to generate the pro- The electron withdrawing substitution in the six-membered tonated monomer was used by injecting methanol radical pyridine ring decreases the proton affinities over a range cations generated in the ion source into the drift cell con- of almost 40 kcal/mol from 222.0 kcal/mol for pyridine taining a 3-F-pyridine/helium mixture. The protonated dimer to 202.9 kcal/mol for 1,3,5-triazine and 182.8 kcal/mol for [(3-F-pyridine) H+] was formed through a series of reactions pentafluoropyridine. These changes in proton affinity may be 2 that generate (3-F-pyridine)H+ followed by the addition of due to effects other than changes in polarizability with alky- the neutral 3-F-pyridine monomer. lation. For example, electron withdrawing substituents may The reactant and product ions exiting the drift cell were form intramolecular dipoles that are repulsive to an added pro- scanned and detected using second quadrupole mass filter and ton, thus lowering the proton affinity of base (B). The electron detector assembly. The arrival time distributions (ATDs) were withdrawing substituents may also place less electron den- collected by monitoring the intensity of each ion as a function sity in the vicinity of the bridging proton leading to a weaker of the drift time, by varying the drift cell voltage that changes bond. These related effects on the proton affinities and dimer the drift time, i.e., reaction time. binding energies can lead to a correlation of decreasing proton affinities and hydrogen bond energies. In these cases, the III. COMPUTATIONAL SECTION increased proton donor strength of the protonated component does not fully compensate for the decreased proton acceptor Density Functional Theory (DFT) computations of the strength of the neutral base caused by the electronegative sub- lowest energy geometries for the various protonated dimers stituents. Here, we shall examine these effects in protonated were performed at the B3LYP/6-311++G∗∗ level of theory

using the Gaussian 03 program suite.35 Vibrational frequency calculations were also performed for all the optimized geometries at the same level of theory in order to obtain zero point vibrational energy (ZPVE) and also to verify the absence of any imaginary frequencies.35 Frequency calculations to mea- sure rotational barriers were performed on non-optimized geometries, which were derived by rotating one cyclic ring in the optimized structure along the N–H axis. The absence of a true ground state as a transition structure for rotation about the hydrogen bond was veriﬁed by the presence of one or more imaginary frequencies. Attempts to optimize these mod- iﬁed structures produced the original ground state geometry. Charge densities were obtained by population analysis using the natural bond orbital method at the B3LYP/6-311++G∗∗ level of theory after the frequency calculations. Corrections to basis set superposition error (BSSE) were made only for the + + (pyrimidine)2H and (3-F-pyridine)2H dimers since these corrections were found to be small (0.4–0.8 kcal/mol).

IV. RESULTS AND DISCUSSION

A. Formation of the protonated pyrimidine dimer + FIG. 1. Mass spectra obtained following the injection of C4H4N2 · The experimental methods above generate associa- (i.e., pyrimidine+· ) into pyrimidine/He in the mobility cell at the + tion/dissociation equilibrium reactions (1) by injecting the temperatures as shown. Note decreasing dimer/monomer ratio I(H (C H N ) /I(H+C H N ) with increasing temperature. Total pressures, P protonated monomer or dimer ion into gas mixtures contain- 4 4 2 2 4 4 2 t (Torr) inside the drift cell are: (a) Pt = 0.70 (pure He); (b) Pt = 0.76, Ppyrim ing the neutral monomer. Equilibrium can be achieved if the = 0.06; (c) Pt = 0.83, Ppyrim = 0.066; (d) Pt = 0.85, Ppyrim = 0.068; (e) Pt = = = = = reactions in both directions are fast enough compared with 0.88, Ppyrim 0.071; (f) Pt 0.92, Ppyrim 0.072; and (g) Pt 0.95, = the ion drift time. At 300 K we observed irreversible asso- Ppyrim 0.073. ciation, but at higher drift cell temperatures dissociation be- + action (1) to form (pyrimidine) H in neat pyrimidine vapor, came fast enough to make the reaction reversible. Figure 1 2 without He, in the cell at Ppyrim = 0.39, 0.59, and 0.75 Torr displays the mass spectra obtained following the injection of − we obtained K = 2623, 2640, and 2603 atm 1, respectively, the pyrimidine radical cation into the drift cell containing He at a cell temperature of 523 K, which are constant within the carrier gas or a pyrimidine/He gas mixture at different tem- experimental error. peratures. At 318 K in the presence of a small concentration The equilibrium constant K was obtained at different of pyrimidine (0.06 Torr), the protonated pyrimidine dimer ◦ ◦ temperatures, and H and S were obtained from the slope is the only ion observed indicating irreversible association. and intercept of the van’t Hoff plot shown in Figure 3(b).All However, as the temperature of the drift cell increases, the measurements were replicated at least three times. The result- protonated monomer is formed by the dissociation of the pro- ◦ ◦ ing H and S values are listed in Table I. tonated dimer. As the temperature increases further, the intensity of the protonated dimer decreases and that of the protonated monomer increases indicating reversible association. Under these conditions the equilibrium constant (K) for reaction (1) is obtained from Eq. (3), + + K = I B2H /I BH P(B), (3) + + where B is the neutral pyrimidine, I[BH ] and I[B2H ]are the integrated signal intensities of the ATDs of the protonated monomer and protonated dimer, respectively, and P(B) is the pressure of the pyrimidine monomer in the drift cell in atm. Equilibrium was checked by ensuring that the following two conditions are satisﬁed: (i) The integrated intensities of the reactant and product ions reach a constant ratio during the residence time in the cell as illustrated in Figure 2. (ii) The ATDs of the reactant and product ions overlap, indicating that the product and reactant ions are coupled reactively by FIG. 2. Time resolved mass scan following the injection of pyrimidineH+ the equilibrium reaction faster than their movement through (m/z 81) into the mobility cell containing 0.59 Torr pyrimidine vapor in 1.30 the cell as shown in Figure 3(a). We also tested that the Torr total pressure in helium at 523 K. Reaction time was varied by varying the cell voltage from 9 V to 33 V. The time proﬁle shows the reversible equilibrium constant K remained constant in the operating + + association of pyrimidineH (m/z 81) + pyrimidine → (pyrimidine)2H ranges of He and pyrimidine pressures. For example, for re- (m/z 161).

+ + FIG. 3. (a) Arrival time distributions (ATDs) for the reversible dissociation of (pyrimidine)2H (m/z 161) into pyrimidineH (m/z 81) + pyrimidine in 0.59 Torr pyrimidine vapor in 1.30 Torr total pressure in helium at 523 K. Overlapping ATDs show that the dissociation/association reaction is in equilibrium. The slow increase of the intensity of the protonated monomer and dimer at early time is due to the formation of the protonated monomer inside the drift cell at different distances as opposed to injecting the protonated monomer at zero time at the entrance of the cell. (b) van’t Hoff plot for association/dissociation + equilibrium forming the protonated dimer (pyrimidine)2H in 0.58 Torr pyrimidine vapor in 1.3 Torr total pressure in He.

TABLE I. Thermochemistry of protonated azines and ﬂuoropyridines and of their protonated dimers.a

◦ + b b ◦ + 27 b Base (B) H dissoc (B2H ), Expt. , Calc. (E) S dissoc (B2H ) Proton afﬁnity (B) (NIST) Proton afﬁnity (B) (Calc.)

Azines Pyridine 25.0c 29.5c 222.0 221.9 24.9 (T-shaped) 22.9 (planar) 1,2-Diazine 29.7 (trans-planar) 216.8 218.1 25.8 (cis-planar) 23.9 (T-shaped) 1,3-Diazine (pyrimidine) 22.1 26.8 211.7 211.3 22.4 (T-shaped) 20.9 (trans-planar) 19.6 (cis-planar) 1,4-Diazine 21.9 (T-shaped) 209.6 208.5 19.8 (planar) 1,3,5-Triazine 19.3 (T-shaped) 202.9 199.7 17.3 (planar) Fluoropyridines 2-F-pyridine 24.8 (planar) 211.4 210.4 23.6 (T-shaped) 3-F-pyridine 23.0 33.0 215.6 214.8 23.3 (T-shaped) 21.5 (planar) 4-F-pyridine 23.0 (T-shaped) 218.2 217.4 20.7 (planar) 2,6-Diﬂuoro-pyridine 23.3 (T-shaped) 199.3 19.4 (planar) Pentaﬂuoro-pyridine 18.1 (T-shaped) 182.8 182.0 15.4 (planar)

a ◦ ◦ Enthalpies and proton afﬁnities in kcal/mol, entropies in cal/mol K. Experimental values in bold. Estimated uncertainties: PAs, ±1 kcal/mol, H dissoc, ±1.2 kcal/mol, and S dissoc, ±1.8 cal/mol K. b + Experimental values (bold) and computational values (PAs and E) from this work unless noted otherwise. Calculated PAs and E(B2H ) are obtained using the DFT B3LYP/6- 311++G∗∗ method. c ◦ + ◦ + 27 H dissoc(pyridine)2H and S dissoc(pyridine)2H average literature values as listed in NIST WebBook.

FIG. 4. DFT calculated structures of the protonated pyrimidine dimer obtained at the B3LYP/6-311++G∗∗ level. Binding energy E in kcal/mol, and the value in brackets is corrected for BSSE. The approximate angle between the plans of the two rings in the T-shaped structure is 90◦.

The B3LYP/6-311++G∗∗ method has been previously 3-F-pyridine undergoes reversible association with the neutral used to accurately compute (within 1.5 kcal/mol) binding en- 3-F-pyridine molecule to form the protonated dimer H+(3- ergies of complexes involving ionized benzene and nitrogen Fpy)2 as shown at higher temperatures where the intensity heterocyclic molecules similar to the present systems.34, 36 of the protonated dimer decreases and that of the protonated This trend continues in the present study not only in the calculations of binding energies but also the proton afﬁnities as evident from the excellent agreement between the calculated and the experimental values listed in Table I. The calculated lowest energy isomer of the proton-bound pyrimidine dimer at the B3LYP/6-311++G∗∗ level has a T-shape geometry with a H-bond distance of 1.6 Å as shown in Figure 4. The calculated binding energy of 22.4 kcal/mol (21.6 corrected for BSSE) is in very good agreement with the measured −H◦ of 22.1 ± 1.2 kcal/mol. The structures and binding energies of two planar structures, obtained by rotation of the pyrimidine molecule about the hydrogen bond ﬁxed at the equilibrium distance of 1.6 Å found in the lowest energy isomer, are also shown in Figure 4. The small difference in the binding energies of the lowest energy T-shape isomer (a) and the trans- planar structure (b) (1.2 kcal/mol) suggests that the two isomers may co-exist if the rotational barrier is low. However, the cis-planar structure (c) can be excluded based on the low binding energy (19.6 kcal/mol) as compared to the experimental value of 22.1 ± 1.2 kcal/mol.

+· B. Formation of the protonated 3-F-pyridine dimer FIG. 5. Mass spectra obtained following the injection of CH3OH into 3-F- pyridine/He that forms (3-F-pyridine)H+ in the mobility cell at the tempera- + + Figure 5 displays the mass spectra obtained at differ- tures shown. Note decreasing dimer/monomer ratio I[H (3-Fpyd)2]/I[H (3- Fpyd)] with increasing temperature. Pressures (Torr) inside the drift cell are: ent temperatures following the injection of the methanol rad- = = = = = +· (a) Pt 2.05, P3Fpyd 0.24; (b) Pt 2.08, P3Fpyd 0.25; (c) Pt 2.04, ical cation (CH3OH ) into the drift cell containing 3-F- P3Fpyd = 0.25; (d) Pt = 2.06, P3Fpyd = 0.25; (e) Pt = 2.07, P3Fpyd = 0.25; (f) pyridine vapor in He carrier gas. The resulting protonated Pt = 2.02, P3Fpyd = 0.25; and (g) Pt = 2.06, P3Fpyd = 0.26.

+ + FIG. 6. (a) Time resolved mass scan of the reversible dissociation of (3-F-pyridine)2H (m/z 195) into 3-F-pyridineH (m/z 98) + 3-F-pyridine in 0.24 Torr of 3-F-pyridine in 2.0 Torr total pressure in helium at 423 K. Drift cell voltage was varied from 13 V to 33 V. Constant ion ratio after 0.0016 s shows that the dissociation/association reaction reached equilibrium in the observed reaction time. (b) van’t Hoff plot for association/dissociation equilibrium forming the + (3-F-pyridine)2H dimer in 0.24 Torr 3-F-pyridine vapor in 2.0 Torr total pressure in He.

monomer increases. Figure 6(a) displays the time-resolved in- C. Formation of the pyrimidine+· (3-F-pyridine) radical tensity proﬁles of the protonated 3-F-pyridine monomer and cation dimer dimer illustrating the approach to equilibrium under the cur- To compare the binding energies of the proton-bound and rent experiemntal conditions. The overalp of the ATDs of the radical cation dimers, we measured H◦ and S◦ for the reactant and product ions conﬁrms that equilibrium has formation of the pyrimidine ·+(3-F-pyridine) radical cation been achieved as shown in Figure S1 of the supplementary dimer under the same experimental conditions used for the material.37 From the slope and intercept of the van’t Hoff ◦ ◦ protonated pyrimidine and 3-F-pyridine dimers. The prim- plot shown in Figure 6(b), H and S values are de- idine radical cation is generated by charge transfer from termined as 23.0 ± 1.2 kcal/mol, and 33 ± 2.0 cal/mol K, · + the injected CH3OH to trace pyrimidne vapor present in respectively. the drift cell. The resulting pyrimidne radical cation un- The calculated lowest energy isomer of the proton-bound dergoes association with the 3-F-pyridine molecule to form ++ ∗∗ + 3-F-pyridine dimer at the B3LYP/6-311 G level has a the pyrimidine · (3-Fyp) radical cation dimer as shown in similar structure to that of the protonated pyrimidine dimer Figure 5. From the slope and intercept of the van’t Hoff with a T-shape geometry and a H-bond distance of 1.6 Å plot shown in Figure 8(a), −H◦ and −S◦ values of 19.2 as shown in Figure 7(a). The calculated binding energy of ± 1 kcal/mol and 27.1 ± 2 cal/mol. K, respectively, are 23.3 kcal/mol (22.6 corrected for BSSE) is in very good determined for the formation of the pyrimidine · +(3-Fyp) − ◦ ± agreement with the measured H of 23.0 1.2 kcal/mol. radical cation dimer. It is clear that measured binding en- The planar structure (Figure 7(b)) obtained by rotation of the ergy for the radical cation dimer is signifcantly lower than 3-F-pyridine molecule about the 1.6 Å hydrogen bond has that of the protonated pyrimidine (22.7 kcal/mol) or 3-F- a binding energy of 21.5 kcal/mol (20.8 kcal/mol corrected pyridine (23.0 kcal/mol) dimers. The difference is mainly due for BSSE) which is lower than the experimental value of to the stronger ion-dipole interaction in the ionic H-bond of 23.0 kcal/mol. the protonated dimer where the proton bridges between two

FIG. 7. DFT calculated structures of the protonated 3-F-pyridine dimer obtained at the B3LYP/6-311++G∗∗ level. Binding energy E in kcal/mol, and the values in brackets are corrected for BSSE. The approximate angle between the plans of the two rings in the T-shaped structure is 90◦.

(a)

(b)

FIG. 8. (a) van’t Hoff plot for association/dissociation equilibrium forming the pyrimidine ·+(3-F-pyridine) radical cation dimer in 0.24 Torr 3-F-pyridine vapor in 2.0 Torr total pressure in He. (b) DFT calculated structures of the pyrimidine ·+(3-F-pyridine) radical cation dimer obtained at the B3LYP/6-311++G∗∗ level. The approximate angles between the plans of the two rings are given in brackets.

nitrogen atoms, and the weaker interaction in the less ionic of 18.5 kcal/mol is in very good agreement with the ex- C–Hδ+...N bond in the radical cation dimer. As shown in perimental value of 19.2 ± 1 kcal/mol. Other higher en- Figure 8(b), the lowest energy isomer of the pyrimidine · +(3- ergy isomers show H-bonding interaction between the C– Fyp) radical cation dimer has a planar structure with a C– H of the 3-F-pyridine molecule and the nitrogen atom Hδ+···N bond length of 1.8 Å between a hydrogen atom of the pyrimidine cation (isomers 2 and 4, Figure 8(b)). of the pyrimidine cation ring and the nitrogen atom of Isomers with perpendicular structures between the two the 3-F-pyridine molecule. The calculated binding energy rings (isomers 2 and 4, Figure 8(b)) have lower binding

energies (15–13 kcal/mol) than the lowest energy isomer 1 (18.5 kcal/mol).

D. Calculations of the binding energies and structures of selected proton-bound dimers The binding energies of further protonated dimers of diazine, triazine, and fluorinated pyridine dimers, and the proton affinities of all the monomers were obtained computationally. Table I shows the results for the lowest energy isomers, and for some isomeric structures with different inter-plane angles between the two rings, corresponding to rotation about the hydrogen bond, which are of interest concerning rotational barriers. The energies of these structures were calculated by restricting the H-bond distance to that found in the lowest energy isomer and allowing rotation of the rings about the hydrogen bond axis. Figures 9 and 10 show the geometries including some bond lengths in the calculated structures. The computed total energies of all the monomers and dimers, including zero point energies, are given in the supplementary material.37 The results in Table I show very good agreement between experiment and theory both for the proton affinities and the dimer bonding energies. The experimental and calculated values agree mostly within ±1.5 kcal/mol, which is comparable to the experimental uncertainty. This suggests that the calculated values for the other species, for which there are no ex- (a) perimental data, may be similarly accurate.

E. Relations between proton affinities and dimer bonding energies, and the effects of internal dipoles As noted above, the hydrogen bonding energies of NH+N homodimers of diverse alkylamines and alkylpyridines remain nearly constant at 24 ± 1 kcal/mol, and similarly, nearly constant at 30 ± 2 kcal/mol for diverse OH+O type homodimers, for bases whose proton affinities vary over 30 kcal/mol.1, 11, 12 In these systems, increasing alkyl substitution increases the polarizabilities and proton affinities, which makes the N lone pairs of the neutral bases stronger hydrogen acceptors but also makes the –NH+ groups of the ions weaker proton donors, keeping the bond energies nearly constant. The present work examines dimers of bases whose proton affinities vary due to a different reason, electron withdrawing N atoms in the ring, or F substituents on the ring. These dimers show different effects from the previously ob- + served constant binding energies of NH N homodimers. In (b) contrast, in the present compounds, the homodimer binding energies vary significantly (Table I and Figures 9 and 10). FIG. 9. DFT calculated structures of the proton-bound dimers of pyri- + + dine, 1,2-diazine, 1,4-diazine, and 1,3,5-triazine obtained at the B3LYP/6- From (pyridine)2H to (pentafluoropyridine)2H ,thePAsof 311++G∗∗ level. The approximate angle between the plans of the two rings the bases decrease by 39.2 kcal/mol and the dimer bind- in the T-shaped structures is 90◦. ing energies decrease by 8.9 kcal/mol. Figure 11 shows the correlation between the calculated proton affinities of the monomer molecules and the binding energies of the proton- 1,4-diazine, and 1,3,5-triazine where the PAs decrease as bound dimers. With the exception of the 1,2-diazine, two 222.0, 218.2, 215.6, 211.7, 209.6, and 202.8 kcal/mol, and groups of bases show strong correlations between the bind- the calculated binding energies (E) of the T-shaped homod- ing energies of the proton-bound dimers and the EA of the imers decrease in the same order, as 24.9. 23.0, 23.3, 22.4, base monomer. The first group (bottom line) includes pyri- 21.9, and 19.3 kcal/mol, respectively. The second group (top dine, 4-F-pyridine, 3-F-pyridine, 1,3-diazine (pyrimidine), line) includes the ortho substituted compounds 2-F-Pyridine,

FIG. 11. Calculated binding energies of the proton-bound dimers and the proton afﬁnities of the monomer molecules. Measured binding energies (this work) are shown in red circles. The top line (dashed blue) includes the ortho substituted compounds 2-F-pyridine, 2,6-di-F-pyridine, and pentaﬂuoropyri- dine.

energies, fall on the same line. The parallel variation of PAs and dimer binding energies may be due to the same physical factors, i.e., electronegative substitution that introduces negatively charged atoms in or on the rings. These negative charge centers and the neighboring positive carbon atoms form inter- (a) nal dipoles. For example, the NBO atomic charges for neutral 1,3-diazine (Figure S2 of the supplementary material)37 show that the C–N–C group (atomic charges 0.281, −0.473, 0.085, respectively) about each nitrogen forms a dipole with the positive end oriented in an angle toward the other negative nitrogen atom. This results in a stabilizing charge–dipole interaction with the neutral molecule, but this stabilizing effect decreases in the protonated molecule. In these ions the charges on the unprotonated C–N–C group remain similar (atomic charges 0.352, −0.405, 0.175) but its dipole now interacts not with a negative second nitrogen but with a nearly neutral protonated N–H+ group (atomic charges −0.465, 0.448). The loss of the stabilizing charge–dipole interaction by protonation increases the energy of the ion and decreases the proton affinity, compared with pyridine that lacks this effect. Similar effects may cause the variation of proton affinities in the order 1,2-diazine > 1,3-diazine > 1,4-diazine, as the internal dipoles align increasingly optimally for stabilizing interactions with the second nitrogen atom in the neutral bases. (b) The internal dipoles that decrease the PAs by this effect can also have a destabilizing effect in the dimer ions, FIG. 10. DFT calculated structures of the proton-bound dimers of selected ∗∗ not directly by affecting the hydrogen bond, but by dipole– fluoropyridine molecules obtained at the B3LYP/6-311++G level. Binding 38 energy E in kcal/mol. The approximate angle between the plans of the two dipole interactions between the component rings. For exam- ◦ + rings in the T-shaped structures is 90 . ple, in the T-shaped isomer of (1,3-diazine)2H the two component rings both contain a C–N–C group dipole of the non- hydrogen-bonding nitrogen (atomic charges 0.309, −0.473, 2,6-di-F-pyridine and pentafluoropyridine. This group will be 0.127 in the neutral component and 0.340, −0.418, 0.154 in discussed under the effects of ortho substitutions below. the protonated component) (see Figure S3 of the supplemen- Figure 11, bottom line, shows that the binding energies of tary material).37 The dipoles point away from each other in the lowest energy T-shaped rotamers of dimers with meta and the T-shaped and planar trans-rotamers, but their axes inter- para substitution, decrease linearly with decreasing PAs of sect in the planar cis-rotamer, making this the highest energy ◦ the monomers. Interestingly, 3-F-pyridine and 4-F-pyridine, (lowest H dissoc) rotamer. Correspondingly, the binding en- where the T-shaped rotamers also have the strongest binding ergies of these rotamers change as planar-cis < planar-trans

< T-shaped, increasing with decreasing repulsion of the inter- ity has compensating effects on the hydrogen donor and ac- nal dipoles. ceptor properties.7, 9, 11–13 This is evidently not enough in the Comparing the T-shaped isomers of the various diazine present bases, where the bond weakening effect of decreas- dimers in Figures 4 and 9, the binding energies are in the order ing basicity of the hydrogen acceptor is not fully compen- 1,2-diazine > 1,3-diazine > 1,4-diazine, which is similar to sated for by the increased hydrogen donor ability of the ion the order that the internal dipoles are aligned closer to the in forming the hydrogen bond. These observed relations be- strongest repulsive 180◦ angle. Here also 1,3,5-triazine with tween the proton affinities of the monomers, the binding en- multiple dipole interactions shows the greatest effect, i.e., the ergies of the dimer ions, and the orientations of the inter- weakest binding energy among the azine dimers. nal dipoles, support the general conclusion that electrostatic charge-dipole and dipole-dipole interactions can determine the relative dimer binding energies for the various diazines 1. Rotation about the hydrogen bond, and relative and triazines. However, there are other complex interactions energies of the rotamers in these protonated and neutral components that require further theoretical analysis. In all the azines in Table I and Figures 4 and 9, except 1,2- diazine, the T-shaped isomers have the lowest energy. This isomer avoids repulsive interactions between the ortho hydro- V. SUMMARY AND CONCLUSIONS gens of the components, which occurs in the planar cis and trans conformations. The various conformations also have The binding energies of homodimers of protonated di- various charge–dipole and dipole–dipole interactions as dis- azines, triazines, and fluropyridines were measured and cal- cussed above. Because of these effects, all the dimers have culated. The binding energies show an unusual trend for ionic different energies in the planar cis and trans, and the T-shaped hydrogen bonded homodimers, in varying significantly with rotamer, differing by 2–4 kcal/mol as Table I and Figures 4 structure and with the proton affinities of the monomers, while and 9 show. Full rotation about the hydrogen bond requires other homodimer ions without the electron-withdrawing sub- passing through all of these conformations and their respec- stituents have constant binding energies over a wide range of tive energies, which creates a barrier of this magnitude to the monomer structures and proton affinities. rotation. These trends can be explained partly by the negatively charged substituent in-ring N or on-ring F atoms, which create internal dipoles. These dipoles can interact attractively with the other negative N atoms in the neutrals, but this stabilizing 2. Effects of ortho substitution interaction is decreased or lost in the protonated ions, result- The top correlation line in Figure 11 that contains or- ing in decreased proton affinities. These dipoles can also in- tho substituted compounds is displaced upward from the bot- teract repulsively between the components of the dimers, de- tom line by bonding energies larger by about 4 kcal/mol. This pending on the relative orientations of the two rings. If these may be due to attractive interaction between the partial pos- PA and binding energy effects are both due to internal dipoles itive charge on the ortho hydrogen of one ring and the neg- in the monomers, this may account for the correlation of de- ative charge on the F substituent of the other ring as shown creasing PAs and decreasing binding energies. In addition, at- + in the “trans” structure of the (2-F-pyridine)2H dimer dis- tractive or repulsive interactions involving atoms in ortho po- played in Figure 10 where the H···F distance is 2.5 Å. Sim- sitions to the hydrogen bond can cause the strongest or weak- ilarly, in the proton-bound dimer of 1,2-diazine, the distance est dimer binding, respectively, in the present dimers. These between the ortho H atom of one ring and the ortho Natom complex effects require detailed theoretical analysis. of the other ring (2.8 Å, Fig. 10) is slightly larger than the distance between the other two N atoms (2.7 Å) involved in the proton sharing (N···H+–N). This stabilizing ortho inter- ACKNOWLEDGMENTS δ+ action can be seen also as stretched C–H –N bonds forming We thank the National Science Foundation (CHE- multiple hydrogen bonded structures. The anomalously large + 0911146) and NASA (NNX08AI46G) for the support of this binding energy of 29.7 kcal/mol for the (1,2-diazine)2H + ◦ work. The authors are grateful to King Abdulaziz University is similar to that of (adenine)2H (H D = 30.3 kcal/mol) + ◦ for the partial support of this work. and (thymine)2H (H D = 30.1 kcal/mol), which were at- tributed to a second hydrogen bond in these complexes, while + 1E. Herbst and E. F. van Dishoeck, Annul. Rev. Astron. 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